CD8+ cytotoxic T lymphocytes (CTL) are immunologic effector cells that have the capacity to specifically recognize and directly kill specific target cells, via interaction of the T cell receptor (TCR) on the CTL surface with peptide/HLA Class 1 complexes on the target cell surface. Beyond relying on naturally elicited CTL, gene transfer of cDNA constructs encoding engineered antigen receptors is an alternate strategy for generating CTL that can be adoptively transferred back to the patient for highly specific therapy. A particularly effective engineered antigen receptor is known as a chimeric antigen receptor (CAR) which directly binds native antigen on the target cell surface and transduces activation signals via immunoreceptor tyrosine-based activation motifs present in the cytoplasmic tails. CAR constructs utilizing an antigen-binding moiety generated from single chain antibodies (scFv) afford the major advantage of being “universal” in that they are HLA class I independent. Most importantly, CD8+ T cells expressing CARs can be adoptively transferred back to the patient where they provide persistent targeted killing of target cells.
Antiretroviral therapy has improved the quality of life for HIV+ individuals and can durably suppress HIV-1 replication. However, efficacy requires strict adherence to treatment regimens and despite undetectable levels of virus in patients' plasma, replication-competent virus persists in chronically infected, long-lived reservoirs in patients. Thus, antiretroviral therapy alone is not curative. This, coupled with the lifelong costs and potential for undesired side effects, have created an impetus for devising a treatment that enables cessation of antiretroviral therapy and there is therefore a need to identify alternative therapies.